MSOT_DMD: Non-invasive Imaging of Muscle Structure in Duchenne Muscular Dystrophy Using Multispectral Optoacoustic Tomography

• Sponsor: University of Erlangen-Nürnberg Medical School (Other)
• Overall Status: Completed
• CT.gov ID: NCT03490214
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 3
• Patients Per Site Per Month: 6.6

Study Details

Study Description

Brief Summary

This pilot study aims to assess subcellular muscle structure in patients with Duchenne X-linked progressive Duchenne muscular dystrophy (DMD) in comparison to healthy volunteers using multispectral optoacoustic tomography (MSOT). During MSOT, a transducer is placed on the skin similar to a conventional sonography and instead of sound, energy is supplied to the tissue by means of light flashes. This leads to a constant change of minimal expansions and contractions (thermoelastic expansion) of individual tissue constituents or molecules. The resulting sound waves can then be detected by the same examination unit.

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy; Muscular Dystrophies; Muscular Dystrophy, Duchenne	Device: Multispectral Optoacoustic Tomography	N/A

Detailed Description

Duchenne X-linked progressive Duchenne muscular dystrophy (DMD) is one of the most common progressive childhood muscle diseases with an incidence of 1 in 3500 male newborns and is associated primarily with decreased life expectancy. From the age of 4-5 years manifest motor problems in everyday life, typical signs of proximal muscle weakness, with lab-chemical increase of the muscle enzyme (creatinine kinase, CK). Within a few years, relevant muscle and tendon shortening leading to joint malpositions and instability, as well as scoliosis and loss of walking around the age of 10 are formed. Supportive therapies can not curatively affect complications and progression of the disease. Pathogenetically, there is a deficiency of dystrophin, a structural protein of the sarcolemma, which is caused by mutations (usually deletions) of the dystrophin gene (Xp21.3-p21.2). The result of dystrophin deficiency is a necrosis of muscle cells that are replaced by connective tissue and adipose tissue. Clinical scores (6-minute walk test, 6MWT) and MRI studies to characterize the degenerative changes of skeletal muscle in the early stages are available for the quantitative assessment of the disease progression as well as therapy effects, the significance of which is controversially discussed. However, the highly sensitive assessment of gene therapy effects (e.g., PTC 124) will become increasingly important in the future. Sensitive, non-invasive methods for the detection of early muscle degeneration and muscle function in the course are of great clinical and scientific importance. The purpose of this first pilot study is to investigate whether the differences in skeletal muscle composition of healthy volunteers and ambulatory patients with early stage DMD can be quantified and characterized using multispectral optoacoustic tomography (MSOT). This could in the future generate a completely new, non-invasive method to develop non-invasive biomarkers of disease progression or therapy response.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Non-invasive Imaging of Muscle Structure in Duchenne Muscular Dystrophy as Diagnostic and Progression Marker Using Multispectral Optoacoustic Tomography
• Actual Study Start Date: Jun 1, 2018
• Actual Primary Completion Date: Aug 1, 2018
• Actual Study Completion Date: Sep 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Muscular Dystrophia Multispectral Optoacoustic Tomography (MSOT) of muscles (left and right, total 8 sites) leg proximal: Musculus quadriceps, distal: Musculus triceps surae arm proximal: Musculus biceps, distal: Musculus brachioradialis	Device: Multispectral Optoacoustic Tomography; Non-invasive transcutaneous imaging of subcellular muscle components
Active Comparator: Healthy Volunteer Multispectral Optoacoustic Tomography (MSOT) of muscles (left and right, total 8 sites) leg proximal: Musculus quadriceps, distal: Musculus triceps surae arm proximal: Musculus biceps, distal: Musculus brachioradialis	Device: Multispectral Optoacoustic Tomography; Non-invasive transcutaneous imaging of subcellular muscle components

Outcome Measures

Primary Outcome Measures

1. Muscular lipid content [Single time point (1 day)]

   Quantitative lipid signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD compared to healthy control Units: arbitrary units (a.u.)

2. Muscular collagen content [Single time point (1 day)]

   Quantitative collagen signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD compared to healthy control Units: arbitrary units (a.u.)

Secondary Outcome Measures

1. Muscular myo-/hemoglobin content [Single time point (1 day)]

   Quantitative myo-/hemoglobin signal derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD compared to healthy control Units: arbitrary units (a.u.)

2. Correlation of lipid signal with age/disease duration [Single time point (1 day)]

   Quantitative lipid signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with individual disease duration/age (in month)

3. Correlation of myo-/hemoglobin signal with age/disease duration [Single time point (1 day)]

   Quantitative moo-/hemoglobin signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with individual disease duration/age (in month)

4. Correlation of lipid signal with 6MWT [Single time point (1 day)]

   Quantitative lipid signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with 6-minute walk test (6MWT, distance in meters, less distance means higher disease severity)

5. Correlation of lipid signal with MRC [Single time point (1 day)]

   Quantitative lipid signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with Medical Research Council (MRC, scale: 0-5, lower score means less muscular strength, measured for each individual muscles) muscle scale

6. Correlation of collagen signal with 6MWT [Single time point (1 day)]

   Quantitative collagen signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with 6-minute walk test (6MWT, distance in meters, less distance means higher disease severity)

7. Correlation of collagen signal with MRC [Single time point (1 day)]

   Quantitative collagen signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with Medical Research Council (MRC, scale: 0-5, lower score means less muscular strength, measured for each individual muscles) muscle scale

8. Correlation of myo-/hemoglobin signal with 6MWT [Single time point (1 day)]

   Quantitative myo-/hemoglobin signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with 6-minute walk test (6MWT, distance in meters, less distance means higher disease severity)

9. Correlation of myo-/hemoglobin signal with MRC [Single time point (1 day)]

   Quantitative myo-/hemoglobin signal (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD correlated with Medical Research Council (MRC, scale: 0-5, lower score means less muscular strength, measured for each individual muscles) muscle scale

10. Signal differences left and right muscles [Single time point (1 day)]

    Comparison of quantitative signal levels (Units: arbitrary units (a.u.)) derived by transcutaneous Multispectral Optoacoustic Tomography (MSOT) in patients with DMD/healthy controls in right and left body muscular groups (upper and lower body)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 10 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

DMD-Patients

Inclusion Criteria:

• Histologic or genetically proven DMD

• Age 3-10 years

Exclusion Criteria:

Healthy controls

Inclusion Criteria:

• Male

• Age 3-10 years

Exclusion Criteria:

• Suspected muscular disease/myopathia

• missing informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen	Erlangen	Bavaria	Germany	91054

Sponsors and Collaborators

• University of Erlangen-Nürnberg Medical School

Investigators

• Principal Investigator: Ferdinand Knieling, Dr., Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen
• Principal Investigator: Regina Trollmann, Prof. Dr., Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Erlangen-Nürnberg Medical School
• ClinicalTrials.gov Identifier: NCT03490214
• Other Study ID Numbers: 67_18 B
• First Posted: Apr 6, 2018
• Last Update Posted: Dec 9, 2019
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Erlangen-Nürnberg Medical School: Optoacoustics; MSOT; Multispectral Optoacoustic Tomography
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne

Study Results

No Results Posted as of Dec 9, 2019